Class: Antimetabolite – Pyrimidine Analog
Mechanism of Action:
- 5-FU is converted intracellularly to active metabolites (e.g., fluorodeoxyuridine monophosphate).
- It inhibits thymidylate synthase, leading to depletion of thymidine triphosphate, essential for DNA synthesis.
- Also incorporates into RNA and DNA, disrupting their function.
- Results in impaired DNA synthesis and repair, causing cell death—especially in rapidly dividing cancer cells.
Indications:
- Colorectal cancer (adjuvant and metastatic)
- Breast cancer (part of CMF, FEC regimens)
- Head and neck cancers
- Gastric cancer
- Other solid tumors (often combined with radiation or other agents)
- Administered IV (bolus or continuous infusion) or topically (for skin cancers).
- Rapidly metabolized primarily by dihydropyrimidine dehydrogenase (DPD) in the liver.
- DPD deficiency can cause severe toxicity.
Dosing:
- Variable depending on regimen—bolus dosing or continuous infusion (e.g., 400–600 mg/m² IV bolus, or continuous infusion over several days).
- Often combined with leucovorin to enhance efficacy.
Common Toxicities:
| Toxicity | Notes/Management |
|---|---|
| Myelosuppression | Neutropenia, thrombocytopenia |
| Mucositis | Mouth and GI tract inflammation |
| Diarrhea | Can be severe; monitor hydration and electrolytes |
| Hand-foot syndrome | Palmar-plantar erythrodysesthesia, especially with continuous infusion or capecitabine |
| Neurotoxicity | Rare, cerebellar syndrome reported |
| Cardiotoxicity | Rare ischemic events (angina, MI) |
Monitoring:
- CBC with differential regularly
- Monitor for signs of mucositis, diarrhea, and hand-foot syndrome
- Assess renal and hepatic function prior to therapy
- Watch for early signs of toxicity in patients with potential DPD deficiency
Drug Interactions:
- Enhanced toxicity with warfarin, phenytoin, and other CYP450 metabolized drugs.
- Leucovorin potentiates 5-FU effects and toxicities.
Pharmacist Practice Pearls:
- Check for DPD deficiency if severe unexpected toxicity occurs.
- Counsel patients on hydration, mouth care, and reporting diarrhea early.
- Recognize differences in toxicity profiles between bolus and continuous infusion.
- Monitor INR closely if on warfarin when starting or stopping 5-FU.
Key Takeaway:
5-FU is a cornerstone antimetabolite chemotherapy drug that disrupts DNA synthesis, widely used across multiple solid tumors. Effective use requires careful toxicity monitoring and patient education to mitigate common adverse effects.